terça-feira, abril 26, 2011

An international team of physicists and neuroscientists has reported a breakthrough in magnetic resonance imaging (MRI) that allows brain scans more than seven times faster than currently possible. In an article published December 20, 2011, in the journal PloS ONE, a University of California (UC) Berkeley (USA; http://berkeley.Edu), physicist and colleagues from the University of Minnesota (Twin Cities [Minneapolis-St. Paul], USA; www.umn.edu) and Oxford University (UK; www.ox.ac.uk) described two developments that allow full three-dimensional (3D) brain scans in less than half a second, instead of the typical two to three seconds.“When we made the first images, it was unbelievable how fast we were going,” said first author Dr. David Feinberg, a physicist and adjunct professor in UC Berkeley’s Helen Wills Neuroscience Institute and president of the company Advanced MRI Technologies (Sebastopol, CA, USA). “It was like stepping out of a prop plane into a jet plane. It was that magnitude of difference.” For neuroscience, in particular, fast scans are vital for capturing the dynamic activity in the brain. “When a functional MRI [fMRI] study of the brain is performed, about 30 to 60 images covering the entire 3D brain are repeated hundreds of times like the frames of a movie but, with fMRI, a 3D movie,” Dr. Feinberg said. “By multiplexing the image acquisition for higher speed, a higher frame rate is achieved for more information in a shorter period of time.” “The brain is a moving target, so the more refined you can sample this activity, the better understanding we will have of the real dynamics of what’s going on here,” added Dr. Marc Raichle, a professor of radiology, neurology, neurobiology, biomedical engineering, and psychology at Washington University in St. Louis (MO, USA; http://wustl.edu), who has followed Dr. Feinberg’s work.Because the technique works on all modern MRI scanners, the impact of the ultrafast imaging technique will be immediate and widespread at research institutions worldwide, according to Dr. Feinberg. In addition to greatly advancing the field of neural imaging, the discovery will have an immediate impact on the Human Connectome Project (http://humanconnectomeproject.org), funded in 2010 by the US National Institutes of Health (NIH; Bethesda, MD, USA) to map the connections of the human brain through fMRI and structural MRI scans of 1,200 healthy adults.“At the time we submitted our grant proposal for the Human Connectome Project, we had aspirations of acquiring better quality data from our study participants, so this discovery is a tremendous step in helping us accomplish the goals of the project,” said Dr. David Van Essen, a neurobiologist at Washington University and coleader of the project. “It’s vital that we get the highest quality imaging data possible, so we can infer accurately the brain’s circuitry – how connections are established, and how they perform.”The faster scans are made possible by combining two technical improvements devised in the past decade that separately increased scanning speeds two to four times over what was already the fastest MRI technique, echo planar imaging (EPI). Physical limitations of each method prevented further speed improvements, “but together their image accelerations are multiplied,” Dr. Feinberg said. The researchers can now obtain brain scans considerably faster than the time reductions reported in their study and many times faster than the capabilities of current machines.Nearly 20 years ago, however, a new type of MRI called functional MRI (fMRI) was developed to highlight areas of the brain using oxygen, and thus seemingly engaged in neuronal activity, such as thinking. Utilizing EPI, fMRI vividly differentiates oxygenated blood funneling into working areas of the brain from deoxygenated blood in less active areas.With EPI, a single pulse of radio waves is used to excite the hydrogen atoms, but the magnetic fields are rapidly reversed several times to elicit about 50 to 100 echoes before the atoms settle down. The multiple echoes provide a high-resolution image of the brain. In 2002, Dr. Feinberg proposed using a sequence of two radio pulses to obtain twice the number of images in the same amount of time. Called simultaneous image refocusing (SIR) EPI, it has proved useful in fMRI and for 3D imaging of neuronal axonal fiber tracks, though the improvement in scanning speed is limited because with a train of more than four times as many echoes, the signal decays and the image resolution decreases.Another acceleration advance, multiband excitation of several slices using multiple coil detection, was proposed in the United Kingdom at about the same time by Dr. David Larkmann for spinal imaging. The technique was used for fMRI by Dr. Steen Moeller and colleagues at the University of Minnesota. This technique, too, had limitations, mainly because the multiple coils are relatively widely spaced and cannot differentiate very closely spaced images.The ability to scan the brain in under 400 ms moves fMRI closer to electroencephalography (EEG) for capturing very rapid sequences of events in the brain. The development will affect general fMRI as well as diffusion imaging of axonal fibers in the brain, both of which are needed to achieve the main goal of the Human Connectome Project. Diffusion imaging reveals the axonal fiber networks that are the main nerve connections between areas of the brain, while fMRI shows which areas of the brain are functionally connected, meaning, which areas are active together or sequentially during various activities.

Osteopoikilosis presents as round or ovoid sclerotic lesions with an appearance like enostosis on pathology. Synovial osteochondromatosis occurs due to cartilaginous metaplasia with synovial villous proliferation with calcified nodules in proximity to joints. A case of osteopoikilosis associated with synovial osteochondromatosis is described. Intraosseus and juxta osseus sclerotic bone lesions were identified on radiographs and computed tomography in a patient with knee pain. The association of osteopoikilosis with synovial osteochondromatosis is rare and to our knowledge has received little attention in the literature.

INTRODUCTIONOsteopoikilosis is a hereditary condition. The hallmark of this condition is numerous discrete or confluent round or ovoid calcific or ossific densities often with minimally spiculated margins, in bones, often in proximity to joints (1). These are often incidentally discovered and pathologically represent bone islands. They are occasionally associated with cutaneous lesions as well as other osteosclerotic disorders (2).Synovial osteochondromatosis is a rare benign monoarticular arthropathy. The inciting stimulus which results in the rapid development of this synovial metaplastic process is unknown (3). An embryonic rest has been hypothesised to be the causative factor for the disease (4, 5). Trauma has also been identified as a precipitating factor (4, 6). A neoplastic basis for the cartilaginous metaplasia within the synovial villi is considered by some authors (3, 4, and 5). Although malignant transformation has been reported occasionally (4, 7, and 8) it is controversial as to whether or not chondrosarcomas actually originate in this entity. Synovial chondromatosis most commonly involves the knee, elbow, and hip in young adults (6, 9). The association of osteopoikilosis with synovial osteochondromatosis is rare and to our knowledge has received little attention in the literature.CASE REPORTA 25 year old man presented to the orthopaedics department in our institution with right knee pain and difficulty in walking, progressively increasing for 5 years. He also gave a history of fall, which happened 1 month before the onset of pain. There was no history of tingling or numbness or significant family history. Outside MRI showed tears of both menisci on the right, longitudinal tear of the lateral meniscus and radial tear of the medial meniscus, along with a tear of the lateral collateral ligament of the right knee. The MR also showed nodular lesions in relation to the knee which were hypointense on all sequences, few of which were intra osseous and few were extra osseous. (Figures 1a-c) The patient did not have any other complaints. Examination of the right lower limb revealed wasting of the quadriceps. Rest of the clinical examination was normal. His laboratory values including erythrocyte sedimentation rate, rheumatoid factor, C-reactive protein, uric acid, serum calcium and parathyroid hormone levels were normal.He was referred to the radiology department for a radiograph of the knee joint, which showed mild juxta-articular osteopenia and multiple small discrete, round, oval, dense calcific lesions in a symmetric distribution (Fig. 2

). These lesions were distributed more in the epiphysis and metaphysis of the femur distally (Fig. 3 ). An AP radiograph of the pelvis did not show any abnormality. All findings were suggestive of osteopoikilosis. There were also few intra articular soft tissue density lesions with peripheral calcifications. A CT scan done thereafter confirmed the findings. (Fig. 4 a and 4c).After the diagnosis, the patient was re-evaluated, and any overlooked pathology was searched. There was no pain or swelling of the joints, no muscle contractures, no soft tissue or skin changes.He underwent an arthroscopic proceed open biopsy of the lateral condyle of the right femur to exclude osteoblastic metastases. Arthroscopy revealed typical features of proliferative frond like synovial disease with associated loose bodies as seen in synovial chondromatosis. A synovial debridement with removal of the loose bodies was done. These were however not sent for histopathological analysis by the operating surgeon in order to reduce patient expenses and because the arthroscopic appearances were typical. Microscopic histopathology revealed few thickened trabeculae merging with normal surrounding bone with no evidence of metastases, which can be seen with osteopoikilosis. We do not have archived pathological images as the femoral condyle biopsy was done to exclude osteoblastic metastases. Images were not archived as it was a negative study for the diagnostic question i.e. metastases.

Osteopoikilosis, also called osteopathia condensans disseminata, or "spotted bone disease" is an incidentally detected disorder characterized by an abnormality in enchondral bone maturation. There is no gender predilection, men and women are equally affected (1, 9). It is usually inherited as an autosomal dominant condition. Osteopoikilosis results in multiple small densities of oval or rounded shape that are symmetrically distributed within the metaphyses and epiphyses of the long bones, in periarticular osseous regions. On histology these foci are formed by dense trabeculae of spongious bone, occasionally forming a nidus without communication with bone marrow. These appear in childhood and persist thereafter (2, 5, 10). Sites of predilection include phalanges (100%), carpal bones (97.4%), metacarpals (92.5%), foot phalanges (87.2%), metatarsals (84.4%), tarsal bones (84.6%), pelvis (74.4%), femur (74.4%), radius (66.7%), ulna (66.7%), sacrum (58.9%), humerus (28.2%), tibia (20.5%), and fibula (2.8%) in one study of 4 families. The ribs, skull and vertebrae are spared (2).Some patients have associated connective tissue nevi called dermatofibrosis lenticularis disseminate, this is called Buschke-Ollendorff syndrome (11). Osteopoikilosis is also associated with keloid formation, dwarfism, spinal stenosis, dystocia, melorrheostosis, tuberous sclerosis and scleroderma (6, 7, and 13). Mixed sclerosing bone dystrophy comprises osteopathia striata and melorheostosis along with osteopoikilosis (2).Differential diagnoses include osteoblastic metastasis, tuberous sclerosis and mastocytosis (1, 9). Blood investigations like alkaline and acid phosphatase and bone scan are typically normal (1, 2, 14).The diagnosis of primary synovial osteochondromatosis is based on the rapid onset of monoarticular pathology in a young adult and on the gross histopathological appearance (3). The typical features are ectopic chondroid matrix formation under the synovium, synovial hyperplasia, multiple small loose bodies and the absence of articular cartilage destruction. However secondary synovial metaplasia occurs in the more common traumatic and degenerative joint disorders (3, 5, and 6). Radiographs may or may not reveal calcific densities.Synovial chondromatosis progresses through various stages of activity (4, 13). In the acute stage, the entire joint synovium is hypertrophied and hyperemic with numerous foci of cartilage formation. Small cartilaginous fragments are extruded into the joint and dystrophic calcification may occur. (3,6) During the intermediate stage, the acute synovial reaction gradually subsides (7,10,13, 15)The free cartilaginous loose bodies undergo degenerative, proliferative (enlargement on multiplication), or resorptive changes, depending on stresses peculiar to the joint involved and location within the joint (4,7). Endochondral bone formation may occur but requires a blood supply and is confined to loose bodies with a pedicle or to free loose bodies that have regained a synovial attachment (4,9).In the late stages of the disease, the generalized synovial reaction reverts to normal. Secondary osteoarthritis results from the presence of loose bodies within the joint in chronic cases (6, 8, 9). This may cause localized secondary synovial chondromatosis, as well as osteochondritic loose bodies formed by detached osteophytes. Therefore, in older cases of long duration only a presumptive diagnosis of primary synovial chondromatosis can be made based on the history and the number and character of the loose bodies.Synovial chondrosarcoma has to be considered in the differential diagnosis of synovial chondromatosis since both lesions may exhibit synovial calcification and atypical multinucleated cartilage cells (9, 13, and 16). The diagnosis of chondrosarcoma is established on the basis of a large, lobulated synovial lesion with extra-articular invasion and histological sections which exhibit numerous multinucleated cartilage cells having bizarre hyperchromatic nuclei. Secondary synovial chondromas, attached or free, which occur in association with traumatic internal derangement and osteoarthritis, are distinguished by the existence of primary joint disease and localized synovial reaction. Traumatic joint surface separations and detached chondro-osteophytes represent true osteochondritic loose bodies and are readily differentiated. Loose bodies resulting from traumatic disruption of epiphyses, joint fibrocartilage or articular cartilage exhibit the gross and histological features of the normal joint structures involved. Chondro-osteophytes, usually no more than two or three in number, are often large and are found in a diseased or arthritic joint.Microscopically they exhibit a periphery of fibrocartilage with underlying cancellous dead bone and a zone of calcification. The classic loose body (osteochondritis dissecans) is most often single and involves an otherwise normal joint. It is distinguished microscopically by a periphery of articular cartilage, fibrotic reparative reaction, and underlying necrotic bone.A close differential of this condition would be melorrheostosis with soft tissue involvement. This condition demonstrates an inner undulating margin encroaching into the medullary cavity with a linear track pattern. Typically there is a wavy cortical hyperostosis in the bone which simulates molten wax flowing down the side of a candle (17, 18). This may have an intra articular extension with or without joint effusion. Heterotopic bone formation and soft tissue calcification can rarely occur. Pathological examination shows variable degree of marrow fibrosis with irregular mixed areas of lamellar and woven bone. This was not seen in our patient.Osteopoikilosis is differentiated from melorrheostosis by symmetrical involvement, a normal scintigraphy, absence of soft tissue involvement, and no related symptomatology. Other differential diagnoses to consider would include myositis ossificans and calcified hematoma. Other sclerosing bone dysplasias encompass Jaffe-Lichenstein disease which is a polyostotic fibrous dysplasia, which shows more frequent osteolytic areas and related histopathological changes.The only other case report describing this association depicted multiple loose bodies in the hip joint and small spherical areas of increased density in keeping with generalized osteopoikilosis. (15). The authors speculated that chondromatosis is the synovial manifestation of osteopoikilosis (synosteopoikilosis). To our knowledge the combination of the two entities has received little attention in literature, although several case reports have described osteopoikilosis and its associations, synovial osteochondromatosis is also an association to bear in mind when evaluating intra articular and juxta articular calcifcations. As reported by Havitcioglu, (15) when osteopoikilosis is detected or suspected, lesions of fibroproliferative origin, should also be sought.

When evaluating intraosseous and extraosseous calcifcations, synovial osteochondromatosis with osteopoikilosis is an association to bear in mind. When osteopoikilosis is detected or suspected, lesions of fibroproliferative origin should also be sought.

25 year old man with osteopoikilosis and synovial osteochondromatosis of the knee. A: AP radiograph of the right knee showing intra osseus and extraosseus juxta articular ossific densities, in the lateral femoral condyle, and posterior intrarticular soft tissues. B: Lateral radiograph of the right knee, lateral view, showing intra osseous and extraosseous juxta articular ossific densities, in the lateral femoral condyle, and posterior intrarticular soft tissues.

Figure 4: Conventional Radiography

25 year old man with osteopoikilosis and synovial osteochondromatosis of the knee. AP radiograph of the pelvis showing no significant abnormality.

Figure 5: Computed Tomography

25 year old man with osteopoikilosis and synovial osteochondromatosis of the knee. Axial CT images without contrast of the right knee in bone window showing A: intra osseous juxtaarticular ossific densities, in the lateral femoral condyle, B: intraosseous and extraosseous juxtaarticular ossific densities, in the lateral femoral condyle, and posterior intrarticular soft tissues and C: extraosseous juxtaarticular ossific densities in the posterior intrarticular soft tissues.

Figure 6: Computed Tomography 25 year old man with osteopoikilosis and synovial osteochondromatosis of the knee. Axial CT images without contrast of the right knee in bone window showing intra osseous juxtaarticular ossific densities, in the lateral femoral condyle.

Figure 7: Computed Tomography )Original size:25 year old man with osteopoikilosis and synovial osteochondromatosis of the knee. Axial CT images without contrast of the right knee in bone window showing intraosseous and extraosseous juxtaarticular ossific densities, in the lateral femoral condyle, and posterior intrarticular soft tissues.

Figure 8: Computed Tomography

Original size:25 year old man with osteopoikilosis and synovial osteochondromatosis of the knee. Axial CT images without contrast of the right knee in bone window showing extraosseous juxtaarticular ossific densities in the posterior intrarticular soft tissues.

Figure 9: Conventional Radiography

Original size:25 year old man with osteopoikilosis and synovial osteochondromatosis of the knee. Lateral radiograph of the right knee, lateral view, showing intra osseous and extraosseous juxta articular ossific densities, in the lateral femoral condyle, and posterior intrarticular soft tissues.

Figure 10: Conventional Radiography

Original size:25 year old man with osteopoikilosis and synovial osteochondromatosis of the knee. AP radiograph of the right knee showing intra osseus and extraosseus juxta articular ossific densities, in the lateral femoral condyle, and posterior intrarticular soft tissues.

Conventional MR imaging of the knee utilizes two-dimensional fast spin-echo (FSE) acquisitions that require imaging at anisotropic resolutions and gaps between excitation slices. These highly anisotropic methods introduce the risk of partial volume artifacts and prevent reformatting of image data in different planes. Three-dimensional volumetric acquisitions at isotropic resolutions overcome these problems, and may increase detection accuracy of pathology in joints imperceptible using 2D methods. A newly developed 3D FSE sequence with extended echo train (3D-FSE-Cube) is currently under investigation for use in diagnostic joint evaluation at 3 T. However, optimal pulse sequence parameters for producing the highest quality images have yet to be determined. To ascertain these values for a particular joint, 10 healthy subjects will receive knee MRIs at 3 T. The imaging parameters repetition time (TR), receiver bandwidth, echo train length and parallel imaging factor will be systematically altered for each subject while maintaining a constant scan time of 5 minutes and isotropic spatial resolution of 0.6 mm. Qualitative measures for blurring and detail and quantitative measures for signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for different tissues will be calculated. Parameter combinations maximizing SNR, CNR, and detail while minimizing blurring will be considered optimal. The optimized 3D acquisition can then be further evaluated with respect to traditional 2D FSE sequences, pre-optimized 3D-FSE-Cube sequences or arthroscopy for detection sensitivity of joint pathology.